The TOR signal transduction cascade controls cellular differentiation in response to nutrients
The TOR signal transduction cascade controls cellular differentiation in response to nutrients
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DOI：
10.1091/mbc.12.12.4103
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发表时间：
2001-12-01
影响因子：
3.3
通讯作者：
Cardenas, ME
中科院分区：
文献类型：
--
作者：
Cutler, NS;Pan, XW;Cardenas, ME
雷帕霉素结合并抑制Tor蛋白激酶，Tor蛋白激酶在从酵母酿酒酵母到人类的营养传感信号转导途径中起作用。在酵母细胞中，Tor通路参与调节细胞对营养素的反应，包括增殖、翻译、转录、自噬和核糖体生物合成。我们在这里报告雷帕霉素抑制假菌丝丝状分化的S。酿酒酵母响应氮限制。Tap 42是一种蛋白磷酸酶调节亚基，过表达Tap 42可以恢复雷帕霉素诱导的假菌丝生长。tap 42 -11突变破坏了假菌丝。分化并使其对雷帕霉素具有抗性。缺乏Tap 42调节的蛋白磷酸酶Sit 4的细胞表现出假菌丝生长缺陷，并对雷帕霉素显着过敏。其他Tap 42调节的磷酸酶的突变对假菌丝分化没有影响。我们的研究结果支持了一个模型，其中假菌丝分化是由一个涉及Tor蛋白激酶和Tap 42-Sit 4蛋白磷酸酶的营养传感途径控制的。MAP激酶或cAMP途径的激活，或Sok 2阻遏物的突变，恢复雷帕霉素处理的细胞中的表达，支持Tor途径与这些已知途径平行作用的模型。不同真菌的丝状体分化也被雷帕霉素阻断，表明Tor信号级联在响应营养物调节丝状体分化中起保守作用。
Rapamycin binds and inhibits the Tor protein kinases, which function in a nutrient-sensing signal transduction pathway that has been conserved from the yeast Saccharomyces cerevisiae to humans. In yeast cells, the Tor pathway has been implicated in regulating cellular responses to nutrients, including proliferation, translation, transcription, autophagy, and ribosome biogenesis. We report here that rapamycin inhibits pseudohyphal filamentous differentiation of S. cerevisiae in response to nitrogen limitation. Overexpression of Tap42, a protein phosphatase regulatory subunit, restored pseudohyphal growth in cells exposed to rapamycin. The tap42-11 mutation compromised pseudohyphal. differentiation and rendered it resistant to rapamycin. Cells lacking the Tap42-regulated protein phosphatase Sit4 exhibited a pseudohyphal growth defect and were markedly hypersensitive to rapamycin. Mutations in other Tap42-regulated phosphatases had no effect on pseudohyphal differentiation. Our findings support a model in which pseudohyphal differentiation is controlled by a nutrient-sensing pathway involving the Tor protein kinases and the Tap42-Sit4 protein phosphatase. Activation of the MAP kinase or cAMP pathways, or mutation of the Sok2 repressor, restored filamentation in rapamycin treated cells, supporting models in which the Tor pathway acts in parallel with these known pathways. Filamentous differentiation of diverse fungi was also blocked by rapamycin, demonstrating that the Tor signaling cascade plays a conserved role in regulating filamentous differentiation in response to nutrients.